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Alpha-1 antitrypsin deficiency and pi*Z allele as important co-factors in the development of liver fibrosis

World Journal of Hepatology 2024年第8期16卷 1099-1110页

作者： Ana Isabel Ferreira Catarina guimarães Vitor Macedo silva Sofia Xavier Joana Magalhães JoséCotter department of gastroenterology Hospital da Senhora da Oliveira-GuimarãesGuimarães 4835-044Portugal Life and Health Sciences Research Institute School of MedicineUniversity of MinhoBraga 4710-057Portugal Life and Health Sciences Research Institute/3B’s PT Government Associate LaboratoryBraga 4710-057Portugal department of pulmonology Hospital Senhora da Oliveira-GuimarãesGuimarães 4835-044Portugal

BACKgROUNd Alpha-1 antitrypsin deficiency(AATd)is a codominant autosomal hereditary condition that predisposes patients to the development of lung and/or liver disease,and pi*Z allele is the most clinically relevant *** To evaluate the impact of clinical parameters and AATd phenotypes,particularly the pi*Z allele,in liver *** Cross-sectional cohort study including consecutive patients with AATd followed in pulmonology or Hepatology *** Included 69 patients,49.3%had pi*MZ phenotype and 10.1%pi**** age≥55 years,age at diagnosis≥41 years and AAT at diagnosisg/dL predicted a nonalcoholic fatty liver disease fibrosis score(NFS)not excluding advanced fibrosis[area under the curve(AUC)=0.840,ppp=0.025].An age≥50 years and age at diagnosis≥41 years predicted a fibrosis-4 index of moderate to advanced fibrosis(AUC=0.831,pppatients with hypertension,type 2 diabetes mellitus(dM),dyslipidaemia,metabolic syndrome,and regular alcohol consumption were more likely to have a NFS not excluding advanced fibrosis(pp=0.002,p=0.008,pp=0.033).patients with at least one pi*Z allele and type 2 dM were 8 times more likely to have liver stiffness measurement≥7.1 kpa(p=0.040).CONCLUSION Risk factors for liver disease in AATd included an age≥50 years,age at diagnosis≥41 years,metabolic risk factors,regular alcohol consumption,at least one pi*Z allele,and AAT value at diagnosisg/*** created an algorithm for liver disease screening in AATd patients to use in primary care,selecting those to be referred to Hepatology consultation.

关键词： Alpha-1 antitrypsin deficiency Liver fibrosis Nonalcoholic fatty liver disease fibrosis score Fibrosis-4 index Liver stiffness measurement

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Obtaining 2d Soil geotechnical profiles from Cokriging Interpolation of Sample data and Electrical Resistivity Tomography (ERT)—Applications in Mass Movements Studies

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International Journal of geosciences 2024年第7期15卷 525-548页

作者： Cassiano Antonio Bortolozo Noel Howley Andy Legg Tristan pryer danielle silva de paula Tatiana Sussel gonçalves Mendes daniel Metodiev Marcio Roberto Magalhães de Andrade Silvio Jorge Coelho Simões Maiconn Vinicius de Moraes Marcio Augusto Ernesto de Moraes Luana Albertani pampuch Rodolfo Moreda Mendes Harideva Marturano Egas Institute of Science and Technology So Paulo State University (UNESP) So Jos dos Campos Brazil Cemaden-National Center for Monitoring and Early Warning of Natural disasters General Coordination of Research and Development So Jos dos Campos Brazil Institute for Mathematical Innovation University of Bath Bath UK department of Mathematical Sciences University of Bath Bath UK

Brazil annually faces significant challenges with mass movements, particularly in areas with poorly constructed housing, inadequate engineering, and lacking sanitation infrastructure. Campos do Jordão, in São paulo state, is a city currently grappling with these issues. This paper details a study conducted within a pilot area in Campos do Jordão, where geophysical surveys and geotechnical borehole data were integrated. The geophysical surveys provided 2d profiles, and samples were collected to analyse soil moisture and plasticity. These datasets were combined using a Cokriging-based model to produce an accurate representation of the subsurface conditions. The enhanced modelling of subsurface variability facilitates a deeper understanding of soil behavior, which can be used to improve landslide risk assessments. This approach is innovative, particularly within the international context where similar studies often do not address the complexities associated with urban planning deficits such as those observed in some areas of Brazil. These conditions, including the lack of proper sanitation and irregular housing, significantly influence the geological stability of the region, adding layers of complexity to subsurface assessments. Adapting geotechnical evaluation methods to local challenges offers the potential to increase the efficacy and relevance of geological risk management in regions with similar socio-economic and urban characteristics.

关键词： Mass Movements geophysics ERT geotechnical Surveys Campos do Jordão Cokriging

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Combinatorial therapies for spinal cord injury repair

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Neural Regeneration Research 2025年第5期20卷 1293-1308页

作者： Carla S.Sousa Andreia Monteiro António J.Salgado Nuno A.silva Life and Health Sciences Research Institute(ICVS) School of MedicineUniversity of MinhoCampus de Gualtar-gualtarBragaPortugal ICVS/3B’s Associate Lab PT Government Associated LabCampus de Gualtar-gualtarBragaPortugal

Spinal cord injuries have profound detrimental effects on individuals, regardless of whether they are caused by trauma or non-traumatic events. The compromised regeneration of the spinal cord is primarily attributed to damaged neurons, inhibitory molecules, dysfunctional immune response, and glial scarring. Unfortunately, currently, there are no effective treatments available that can fully repair the spinal cord and improve functional outcomes. Nevertheless, numerous pre-clinical approaches have been studied for spinal cord injury recovery, including using biomaterials, cells, drugs, or technological-based strategies. Combinatorial treatments, which target various aspects of spinal cord injury pathophysiology, have been extensively tested in the last decade. These approaches aim to synergistically enhance repair processes by addressing various obstacles faced during spinal cord regeneration. Thus, this review intends to provide scientists and clinicians with an overview of pre-clinical combinatorial approaches that have been developed toward the solution of spinal cord regeneration as well as update the current knowledge about spinal cord injury pathophysiology with an emphasis on the current clinical management.

关键词： electric stimulation neural tissue regeneration neuroprotection polytherapy spinal cord injury

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Effect of aflibercept combined with triamcinolone acetonide on aqueous humor growth factor and inflammatory mediators in diabetic macular edema

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International Journal of Ophthalmology(English edition) 2024年第2期17卷 297-303页

作者： de-Shuang Li Hong-Xia Liao Jing-Lin Zhang Bo Qin Shenzhen Aier Eye Hospital Aier Eye HospitalJinan UniversityShenzhen 518031Guangdong ProvinceChina guangzhou Aier Eye Hospital Jinan UniversityGuangzhou 510040Guangdong ProvinceChina

AIM:To investigate the efficacy of aflibercept combined with sub-tenon injection of triamcinolone acetonide(TA)in treating diabetic macular edema(dME)and to examine changes in growth factors and inflammatory mediator levels in aqueous humor after ***:Totally 67 dME patients(67 eyes)and 30 cataract patients(32 eyes)were enrolled as the dME group and the control group,*** dME group was divided into the aflibercept group(34 cases)and the aflibercept combined with TA group(combined group,33 cases).The aqueous humor of both groups was collected during the study *** aqueous levels of vascular endothelial growth factor(VEgF),monocyte chemoattractant protein-1(MCp-1),interleukin-6(IL-6),interleukin-8(IL-8),and interleukin-1β(IL-1β)were detected using a microsphere suspension array technology(Luminex 200TM).Aqueous cytokines,best-corrected visual acuity(BCVA),central macular thickness(CMT),and complications before and after treatment were compared between the aflibercept group and combined ***:The concentrations of VEgF,MCp-1,IL-6,and IL-8 in the aqueous humor were significantly higher in the dME group than those of the control group(all pgery,the concentrations of VEgF,MCp-1,IL-6,and IL-8 in the aqueous humor were significantly lower in the combined group than those of the aflibercept group(all pd CMT values of the two groups were statistically different after 1 and 2mo of treatment(pdifference was not statistically significant after 3mo of treatment(p>0.05).CONCLUSION:The cytokines VEgF,MCp-1,IL-6,and IL-8 in the aqueous humor of dME patients are significantly *** and aflibercept combined with TA have good efficacy in dME patients,can effectively reduce CMT,improve the patient’s vision,and have high *** combined with TA can quickly downregulate the aqueous humor cytokines and help to relieve macular edema ***,the long-term eff

关键词： diabetic macular edema aqueous humor cytokines aflibercept triamcinolone acetonide

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Selection of digital fabrication technique in the construction industry--A multi-criteria decision-making approach

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Frontiers of Structural and Civil Engineering 2024年第7期18卷 977-997页

作者： M.p.SALAIMANIMAgUdAM J.JAYApRAKASH department of Structural and geotechnical Engineering School of Civil EngineeringVellore Institute of TechnologyVellore 632014India

digital fabrication techniques,in recent decades,have provided the basis of a sustainable revolution in the construction ***,selecting the digital fabrication method in terms of manufacturability and functionality requirements is a complex *** paper presents alternatives and criteria for selection of digital fabrication techniques by adopting the multi-criteria decision-making *** alternatives considered in the study are concrete three-dimensional(3d)printing,shotcrete,smart dynamic casting,material intrusion,mesh molding,injection concrete 3d printing,and thin forming *** criteria include formwork utilization,reinforcement incorporation,geometrical complexity,material enhancement,assembly complexity,surface finish,and build *** demonstrates different multi-criteria decision-making techniques,with both subjective and objective weighting *** given ranking is based on the current condition of digital fabrication in the construction *** study reveals that in the selection of digital fabrication techniques,the criteria including reinforcement incorporation,build area,and geometrical complexity play a pivotal role,collectively accounting for nearly 70% of the overall *** the evaluated techniques,concrete 3d printing emerged as the best performer,however the shotcrete and mesh molding techniques in the second and third positions.

关键词： digital fabrication multicriteria decision-making concrete 3d printing

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ground-based and additional science support for SMILE

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Earth and planetary physics 2024年第1期8卷 275-298页

作者： J.A.Carter M.dunlop C.Forsyth K.Oksavik E.donovon A.Kavanagh S.E.Milan T.Sergienko R.C.Fear d.g.Sibeck M.Connors T.Yeoman X.Tan M.g.g.T.Taylor K.McWilliams J.gjerloev R.Barnes d.d.Billet g.Chisham A.dimmock M.p.Freeman d.-S.Han M.d.Hartinger S.-Y.W.Hsieh Z.-J.Hu M.K.James L.Juusola K.Kauristie E.A.Kronberg M.Lester J.Manuel J.Matzka I.McCrea Y.Miyoshi J.Rae L.Ren F.Sigernes E.Spanswick K.Sterne A.Steuwer T.Sun M.-T.Walach B.Walsh C.Wang J.Weygand J.Wild J.Yan J.Zhang Q.-H.Zhang planetary Sciences group School of Physics and AstronomyUniversity of LeicesterUniversity RoadLeicesterLE17RHUK Rutherford Appleton Laboratory Space Science Technology Facilities CouncilOxfordshireUK School of Space and Environment Beihang UniversityBeijing 100191China Key Laboratory of Space Environment Monitoring and Information processing Ministry of Industry and Information TechnologyBeijing 100017China department of Space and Climate physics UCLMullard Space Science LaboratoryHolmbury St.MaryDorkingSurreyRH56NTUK Birkeland Centre for Space Science Department of Physics and Technology.University of BergenBergenNorway department of physics and Astronomy University of Calgary2500 University DriveCalgaryAlbertaCanada T2N 1N4 British Antarctic Survey CambridgeUK Swedish Institute of Space physics KirunaSweden West Highfield Campus University of SouthamptonUniversity RoadSO171BJUK goddard Space Flight Center NASAGreenbeltMarylandUSA Athabasca University AthabascaCanada ESTEC European Space AgencyNetherlands University of Saskatchewan SaskatoonCanada The Johns Hopkins University Applied physics Laboratory LaurelMarylandUSA Swedish Institude of Space physics UppsalaSE 75121Sweden Tongji University Shanghai 200092China Center for Space plasma physics Space Science Institute4765 Walnut Street Suite BBoulderColorado80301USA polar Research Institute of China Shanghai 200136China Finnish Meteorological Institute(FMI) Finland department of Earth and Environmental Sciences(geophysics) Ludwig Maximilian University of Munich(LMU)MunichTheresienstr.41MunichD-80333Germany Canadian Space Agency MontrealCanada gFZ german Research Centre for geosciences PotsdamGermany Nagoya University Institute for Space Earth Environment ResearchCenter for Integrated Data ScienceNagoyaAichiJP 464-8601 Northumbria University Newcastle upon TyneTyne and WearUK NE18ST National Space Science Center Chinese Academy SciencesBeijing 100190China Arctic geophysics University Centre in Svalbard

The joint European Space Agency and Chinese Academy of Sciences Solar wind Magnetosphere Ionosphere Link Explorer(SMILE)mission will explore global dynamics of the magnetosphere under varying solar wind and interplanetary magnetic field conditions,and simultaneously monitor the auroral response of the Northern Hemisphere *** these large-scale responses with medium and fine-scale measurements at a variety of cadences by additional ground-based and space-based instruments will enable a much greater scientific impact beyond the original goals of the SMILE ***,we describe current community efforts to prepare for SMILE,and the benefits and context various experiments that have explicitly expressed support for SMILE can offer.A dedicated group of international scientists representing many different experiment types and geographical locations,the ground-based and Additional Science Working group,is facilitating these *** include constructing an online SMILE data Fusion Facility,the discussion of particular or special modes for experiments such as coherent and incoherent scatter radar,and the consideration of particular observing strategies and spacecraft *** anticipate growing interest and community engagement with the SMILE mission,and we welcome novel ideas and insights from the solar-terrestrial community.

关键词： magnetosphere ionosphere magnetosphere-ionosphere coupling ground-based experimentation SMILE conjunctions missions

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Organizational ambidexterity, open innovation and innovation outputs: How do followers and low-flyer EU countries innovate?

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International Journal of Innovation Studies 2024年第2期8卷 186-235页

作者： Joao Leitao Sonia de Brito dina pereira Faculty of Social and Human Sciences NECE-Research Unit in Business SciencesUniversity of Beira Interior6200-001CovilhaPortugal Research Unit in Business Sciences(NECE) University of Beira InteriorCovilhaPortugal Centre for Management Studies of Instituto Superior Tecnico(CEg-IST) University of Lisbon1649-004LisboaPortugal Instituto de Ciencias Sociais ICsUniversity of Lisbon1649-004LisboaPortugal

This study analyses the role played by organizational ambidexterity and open innovation in innovation outputs,considering business units with different levels of technological intensity(medium-high and high tech,and medium-low and low tech)for countries with different inno-vation *** countries considered in this paper are i)Estonia and Slovenia as innovation followers;i)Slovakia,Hungary,Spain,Czech Republic,Italy,portugal,Norway,and Croatia as moderate innovators;and ii)Bulgaria,Lithuania and Romania as modest *** the empirical approach,the research hypotheses arise from the literature review and are tested using secondary data collected from the Community Innovation Survey(CIS)*** conceptual model is tested using the logistic regression method,which indicates suitable accuracy and reliability for empirical testing *** evidence reveals that for innovation followers,ambidexterity has a greater influence on the practice of eco-innovation,marketing innovation,and product *** moderate innovators,ambidexterity has a greater influence on the practice of product innovation,process innovation,and *** modest in-novators,ambidexterity has a greater influence on the practice of product innovation,process innovation,and *** regard to open innovation,for innovation followers,this has a negative influence on product innovation in medium-high and high-tech *** moderate innovators,open innovation has a greater influence in process,organizational,and *** the case of modest innovators,open innovation is more significant for innovation outputs in product,organizational,and marketing *** is not always positively related to innovation outputs.

关键词： Organizational ambidexterity CIS Cooperation Open innovation public innovation policies

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Comparative analysis of microstructure,mechanical,and corrosion properties of biodegradable Mg-3Y alloy prepared by selective laser melting and spark plasma sintering

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Journal of Magnesium and Alloys 2024年第4期12卷 1496-1510页

作者： p.Minárik M.Zemková S.Šašek J.dittrich M.Knapek F.Lukáˇc d.Koutný J.Jaroš R.Král Faculty of Mathematics and physics Charles UniversityKe Karlovu 5Praha 12116Czech Republic Research Centre University ofŽilinaUniverzitná8215/1Žilina 01026Slovakia Institute of plasma physics of the Czech Academy of Sciences Za Slovankou 1782/318200 Praha 8Czech Republic Institute of Machine and Industrial design Brno University of TechnologyTechnická2896/2Brno 61669Czech Republic

This work explored possibilities of biodegradable magnesium alloy Mg-3Y preparation by two modern powder metallurgy techniques–spark plasma sintering(SpS)and selective laser melting(SLM).The powder material was consolidated by both methods utilising optimised parameters,which led to very low porosity(∼0.3%)in the SLM material and unmeasurably low porosity in the SpS *** main aim of the study was the thorough microstructure characterisation and interrelation between the microstructure and the functional properties,such as mechanical strength,deformability,and corrosion *** materials showed comparable strength of∼110 Mpa in tension and compression and relatively good deformability of∼9%and∼21%for the SLM and SpS materials,*** corrosion resistance of the SpS material in 0.1 M NaCl solution was superior to the SLM one and comparable to the conventional extruded *** digital image correlation during loading and the cross-section analysis of the corrosion layers revealed that the residual porosity and large strained grains have the dominant negative effect on the functional properties of the SLM *** the other hand,one of the primary outcomes of this study is that the SpS consolidation method is very effective in the preparation of the W3 biodegradable alloy,resulting in material with convenient mechanical and degradation properties that might find practical applications.

关键词： Magnesium Yttrium powder metallurgy Microstructure Mechanical strength Corrosion resistance

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Role of marine natural products in the development of antiviral agents against SARS‑CoV‑2:potential and prospects

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Marine Life Science & Technology 2024年第2期6卷 280-297页

作者： d.p.Nagahawatta N.M.Liyanage Thilina U.Jayawardena H.H.A.C.K.Jayawardhana Seong‑Hun Jeong Hyung‑Jun Kwon You‑Jin Jeon department of Marine Life Sciences Jeju National UniversityJeju 690-756Republic of Korea department of Chemistry Biochemistry and PhysicsUniversitédu QuébecàTrois-RivièresTrois-RivièresQC G8Z 4M3Canada Marine Science Institute Jeju National UniversityJeju 63333Republic of Korea Functional Biomaterial Research Center Korea Research Institute of Bioscience and BiotechnologyJeongeup-siRepublic of Korea

A novel coronavirus,known as severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),has surfaced and caused global concern owing to its ***-CoV-2 is the causative agent of coronavirus disease 2019;however,it was only discovered at the end of the year and was considered a pandemic by the World Health ***,the develop-ment of novel potent inhibitors against SARS-CoV-2 and future outbreaks is urgently *** naturally occurring bioactive substances have been studied in the clinical setting for diverse *** intricate infection and replication mechanism of SARS-CoV-2 offers diverse therapeutic drug targets for developing antiviral medicines by employing natural products that are safer than synthetic *** natural products(MNps)have received increased attention in the development of novel drugs owing to their high diversity and ***,this review article investigates the infection and replication mechanisms,including the function of the SARS-CoV-2 genome and ***,we highlighted anti-SARS-CoV-2 therapeutic intervention efforts utilizing MNps and predicted SARS-CoV-2 inhibitor design.

关键词： SARS-CoV-2 Marine natural products drug targets Inhibitors

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Maternal supplementation with n-3 fatty acids affects placental lipid metabolism, inflammation, oxidative stress, the endocannabinoid system, and the neonate cytokine concentrations in dairy cows

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Journal of Animal Science and Biotechnology 2024年第05期 2012-2030页

作者： priscila dos Santos silva gitit Kra Yana Butenko Jayasimha Rayalu daddam Yishai Levin Maya Zachut department of Ruminant Science Institute of Animal Sciences ARO Volcani Institute department of Animal Science The Robert H.Smith Faculty of Agriculture Food and Environment The Hebrew University of Jerusalem department of Animal Sciences Michigan State University The Nancy and Stephen grand Israel National Center for personalized Medicine Weizmann Institute of Science

Background The placenta plays a crucial role in supporting and influencing fetal development. We compared the effects of prepartum supplementation with omega-3(n-3) fatty acid(FA) sources, flaxseed oil(FLX) and fish oil(FO), on the expression of genes and proteins related to lipid metabolism, inflammation, oxidative stress, and the endocannabinoid system(ECS) in the expelled placenta, as well as on FA profile and inflammatory response of neonates. Late-pregnant Holstein dairy cows were supplemented with saturated fat(CTL), FLX, or FO. placental cotyledons(n = 5) were collected immediately after expulsion, and extracted RNA and proteins were analyzed by RTpCR and proteomic analysis. Neonatal blood was assessed for FA composition and concentrations of inflammatory *** FO increased the gene expression of fatty acid binding protein 4(FABp4), interleukin 10(IL-10), catalase(CAT), cannabinoid receptor 1(CNR1), and cannabinoid receptor 2(CNR2) compared with CTL placenta. gene expression of ECS-enzyme FA-amide hydrolase(FAAH) was lower in FLX and FO than in CTL. proteomic analysis identified 3,974 proteins; of these, 51–59 were differentially abundant between treatments(p ≤ 0.05, |fold change| ≥ 1.5). Top canonical pathways enriched in FLX vs. CTL and in FO vs. CTL were triglyceride metabolism and inflammatory processes. Both n-3 FA increased the placental abundance of FA binding proteins(FABps) 3 and 7. The abundance of CNR1 cannabinoid-receptor-interacting-protein-1(CNRIp1) was reduced in FO vs. FLX. In silico modeling affirmed that bovine FABps bind to endocannabinoids. The FLX increased the abundance of inflammatory Cd44-antigen and secreted-phosphoprotein-1, whereas prostaglandin-endoperoxide synthase 2 was decreased in FO vs. CTL placenta. Maternal FO enriched neonatal plasma with n-3 FAs, and both FLX and FO reduced interleukin-6 concentrations compared with *** Maternal n-3 FA from FLX and FO differentially affected the bovine placenta; both e

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